The goal of this proposal is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with pharmacotherapy (fluoxetine) in the rehabilitation of post-stroke subjects. This research will help to reveal the relationship between function restorations via pharmacological intervention when combined with noninvasive neuromodulation in patients after ischemic stroke. Stroke is the leading cause of disability in the United States (Nowak et al., 2009) According to the American Heart Association, over 795,000 people experience stroke annually in the USA (Lloyd-Jones et al., 2009). Unfortunately, restitution of post-stroke motor function is frequently incomplete, with the majorit of stroke patients unable to perform professional duties or activities of daily living by six month after their stroke (Hummel and Cohen, 2006). Currently, there are only a few treatments available to improve motor function in stroke; most of them are based on motor learning strategies. Although these treatments may improve motor function significantly, their effects are often limited. The general objective of this research project is to assess the clinical and neurophysiological properties of rTMS and fluoxetine to promote motor recovery in post-stroke subjects as indexed by clinical motor function scales. This will be done by delivering low-frequency rTMS over the brain primary motor cortex (M1) in the unaffected hemisphere while the subjects are receiving fluoxetine treatment, subjects will be assessed at one and three months post intervention. Finally, we will investigate the mechanisms of this treatment by studying the induced neurophysiological and functional changes. This will be indexed by motor evoked potentials, cortical excitability/inhibition measurements, transcallosal inhibition evaluation, and paired associative stimulation. Regarding assurance of success, this proposal has two main specific aims: Aim 1: To determine whether low-frequency rTMS associated with fluoxetine offers additional benefits on motor rehabilitation and retention of motor skills, than pharmacotherapy alone. Aim 2: To determine the effects on cortical excitability when rTMS is combined with pharmacotherapy, whether fluoxetine is capable to induce positive or negative effects in M1 neuromodulation.